The current 'epidemic'of obesity has been called one of the leading public health concerns worldwide. Despite recent progress in the discovery of discrete hypothalamic peptide systems that control food intake, little is known about the manner in which cognitive/affective processing coordinates with hypothalamic energy balance systems to control behavioral output. Hence, this proposal focuses on characterizing functional interactions between the medial prefrontal cortex, a brain region mediating 'executive'control over behavioral output and affective responses, and hypothalamic substrates mediating the homeostatic control of feeding. This proposal is informed by our recent discovery of a novel, specific role of medial prefrontal cortex (mPFC) in controlling feeding microstructure. We find that producing temporary lesions in mPFC fundamentally alters the manner in which rats organize behavioral responses with respect to ingestive behavior. We aim to investigate the behavioral mechanisms and anatomical specificity associated with this effect, and to examine how inactivating mPFC influences the response to hypothalamic administration of orexigenic and anorexic peptides. To obtain a functional anatomical correlate of these behavioral studies, we will investigate the manner in which temporary lesions of the mPFC alter brain activation (measured using Fos expression) associated with feeding. Relevance to public health: These studies have the potential to reveal how the parts of the brain controlling decision-making and impulsivity (such as the prefrontal cortex) can interact with, and perhaps overwhelm, the systems that regulate food intake in response to energy needs. This could lead to fundamentally dysregulated feeding behavior. It is interesting that brain imaging studies have shown alterations in prefrontal cortex function in association with eating disorders and obesity. Our work may help understand how these cortical alterations are ultimately translated into behavioral changes.